Hostname: page-component-76fb5796d-vvkck Total loading time: 0 Render date: 2024-04-26T12:49:37.762Z Has data issue: false hasContentIssue false
  • English
  • Français

Current Concepts in the Prevention of Alzheimer's Disease

Published online by Cambridge University Press:  07 November 2014

Mary Sano
Get access Rights & Permissions [Opens in a new window]

Abstract

Alzheimer's disease represents a significant challenge to the aging population. Since most estimates suggest that AD has a multifactorial etiology, the challenge to find preventative approaches is particularly great. With the aging of the population and the very high incidence from the eighth decade on, the challenge is further enhanced by the need to think of relatively safe interventions given the relative frailty of this elderly population. The need to find safe treatments, or ones with well-understood safety profiles, has led to the examination of known agents for potential dementia-preventing properties. Data supporting these interventions comes from observational studies, laboratory analyses, and clinical trials. Potential mechanisms for prevention of AD include anti-inflammatory and antioxidant approaches. Modulation of risk factors associated with cardiac disease may also reduce the risk of AD. Known agents have been examined for their potential to modify amyloid pathology. Trial designs to address prevention of AD include both primary and secondary prevention studies as well designs to assess slowing disease progression. Information can also be gathered when dementia evaluation is added to ongoing studies. As results from these studies becoming available, we will be able to refine our approach to managing this disease.

Type
Review
Information
CNS Spectrums , Volume 8 , Issue 11: Alzheimer's Disease in the 21st Century , November 2003 , pp. 846 - 853
Copyright
Copyright © Cambridge University Press 2003

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

1.Brookmeyer, R, Gray, S, Kawas, C. Projections of Alzheimer's disease in the United States and the public health impact of delaying disease onset. Am J Public Health. 1998;88:1337–1342.CrossRefGoogle ScholarPubMed
2.Torian, L, Davidson, E, Fulop, G, Sell, L, Fillit, H. The effect of dementia on acute care in a geriatric medical unit. Int Psychogeriatr. 1992;4:231–239.CrossRefGoogle Scholar
3.Kirschstein, R. Disease-specific estimates of direct and indirect costs of illness and NIH support. National Institutes of Health Web site. Available at: http://wwwl.od.nih.gov/osp/ospp/ecostudies/COIreportweb.htm. Accessed June 11, 2002.Google Scholar
4.McDaid, D. Estimating the cost of informal care for people with Alzheimer's disease: methodological and practical challenges. Int J Geriatr Psychiatry. 2001;16:400–405.CrossRefGoogle ScholarPubMed
5.Mudher, A, Lovestone, S. Alzheimer's disease-do tauists and baptists finally shake hands? Trends Neurosci. 2002;25:22–26.CrossRefGoogle ScholarPubMed
6.Wenk, GL, McGann, K, Mencarelli, A, Hauss-Wegrzyniak, B, Del Soldato, P, Fiorucci, S. Mechanisms to prevent the toxicity of chronic neuroinflammation on forebrain cholinergic neurons. Eur J Pharmacol. 2000;402:77–85CrossRefGoogle ScholarPubMed
7.Sano, M. Prevention of Alzheimer's disease: the problem of the drugs and the designs. Curr Neurol Neurosci Rep. 2002;2:392–399.CrossRefGoogle Scholar
8.Sano, M, Ernesto, C, Thomas, RG, et al. A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer's disease. The Alzheimer's Disease Cooperative Study. N Engl J Med 1997;336:1216–1222.CrossRefGoogle ScholarPubMed
9.Marder, K, Sano, M. Estrogen to treat Alzheimer's disease: too little, too late? So what's a woman to do? Neurology. 2000;54:2035–2037.CrossRefGoogle ScholarPubMed
10.Aisen, PS, Schafer, KA, Grundman, M, et al. Effects of rofecoxib or naproxen vs placebo on Alzheimer's disease progression: a randomized controlled trial. JAMA. 2003;289:2819–2826.CrossRefGoogle ScholarPubMed
11.Butterfield, DA. Amyloid beta-peptide (1-42)-induced oxidative stress and neurotoxicity: implications for neurodegeneration in Alzheimer's disease brain. A review. Free Radic Res. 2002;36:1307–1313.CrossRefGoogle ScholarPubMed
12.Morris, MC, Evans, DA, Bienias, JL, et al. Dietary intake of antioxidant nutrients and the risk of incident Alzheimer's disease in a biracial community study. JAMA. 2002;287:3230–3237.CrossRefGoogle Scholar
13.Engelhart, MJ, Geerlings, MI, Ruitenberg, A, et al. Dietary intake of anti-oxidants and risk of Alzheimer's disease. JAMA. 2002;287:3223–3229.CrossRefGoogle Scholar
14.Sano, M. Do dietary anti-oxidants prevent Alzheimer's disease. Lancet Neural. 2002;1:343.CrossRefGoogle ScholarPubMed
15.Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of antioxidant vitamin supplementation in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002;360:23–33.CrossRefGoogle Scholar
16.Kieburtz, K, McDermott, M, Como, P, et al. The effect of deprenyl and tocopherol on cognitive performance in early untreated Parkinson's disease. Parkinson Study Group. Neurology. 1994;44:1756–1759.CrossRefGoogle ScholarPubMed
17. Prevention of Alzheimer's Disease by Vitamin E and Selenium (PREADVISE). Available at: www.Clinicaltrials.gov/ct/show/NCT000040378. Accessed September 6, 2003.Google Scholar
18.Scholtyssek, H, Damerau, W, Wessel, R, Schimke, I. Antioxidative activity of ginkgolides against superoxide in an aprotic environment. Chem Biol Interact. 1997;106:83–90.CrossRefGoogle Scholar
19.Barkats, M, Venault, P, Christen, Y, Cohen-Salmon, C. Effect of long-term treatment with EGb 761 on age-dependent structural changes in the hippocampi of three inbred mouse strains. Life Sciences. 1995;56:213–222.CrossRefGoogle ScholarPubMed
20.van Dongen, MC, van Rossum, E, Kessels, AG, Sielhorst, HJ, Knipschild, PG. The efficacy of ginkgo for elderly people with dementia and age-associated memory impairment: new results of a randomized clinical trial. J Am Geriatr Soc. 2000;48:1183–1194.CrossRefGoogle ScholarPubMed
21. Ginkgo Biloba Prevention Trial in Older Individuals, RFA: AT-99-001, National Center for Complementary and Alternative Medicine and National Institute on Aging, February 26, 1999.Google Scholar
22.Perenboom, RJ, Boshuizen, HC, Breteler, MM, Ott, A, Van de Water, HP. Dementia-free life expectancy (DemFLE) in The Netherlands. Soc Sci Med. 1996;43:1703–1707.CrossRefGoogle ScholarPubMed
23.Toran-Allerand, CD, Miranda, RC, Bentham, WD, et al. Estrogen receptors colocalize with low-affinity nerve growth factor receptors in cholinergic neurons of the basal forebrain. Proc Natl Acad Sci U S A. 1992;89:4668–4672.CrossRefGoogle ScholarPubMed
24.Gould, E, Woolly, CS, Frankfurt, M, McEwen, BS. Gonadal steroids regulate dendritic spine density in hippocampal pyramidal cells in adulthood. J Neurosci. 1990;10:286–1291.CrossRefGoogle ScholarPubMed
25.Xu, H, Sweeney, D, Wang, R, et al. Generation of Alzheimer's betaamyloid protein in the trans-Golgi network in the apparent absence of vesicle formation. Proc Natl Acad Sci U S A. 1997;94:3748–3752.CrossRefGoogle ScholarPubMed
26.Petanceska, SS, Nagy, V, Frail, D, Gandy, S. Ovariectomy and 17 beta-estradiol modulate the levels of Alzheimer's amyloid beta peptides in brain. Exp Gerontol. 2000;35:1317–1325.CrossRefGoogle ScholarPubMed
27.Yaffe, K, Sawaya, G, Lieberburg, I, Grady, D. Estrogen therapy in postmenopausal women: effects on cognitive function and dementia. JAMA. 1998;279:688–695.CrossRefGoogle ScholarPubMed
28.LeBlanc, ES, Janowsky, J, Chan, BK, Nelson, HD. Hormone replacement therapy and cognition: systematic review and metaanalysis. JAMA. 2001;285:1489–1499.CrossRefGoogle ScholarPubMed
29.Wang, PN, Liao, SQ, Liu, RS, et al. Effects of estrogen on cognition, mood, and cerebral blood flow in AD: a controlled study. Neurology. 2000;54:2061–2066CrossRefGoogle Scholar
30.Henderson, VW, Paganini-Hill, A, Miller, BL, et al. Estrogen for Alzheimer's disease in women: randomized, double-blind, place-bo-controlled trial. Neruology. 2000;54:295–301.CrossRefGoogle Scholar
31.Mulnard, R, Cotman, CW, Kawas, C, et al. Estrogen replacement therapy for treatment of mild to moderate Alzheimer's disease: a randomized controlled trial. Alzheimer's Disease Cooperative Study. JAMA. 2000;283:1007–1015.CrossRefGoogle ScholarPubMed
32.Grady, D, Yaffe, K, Kristof, M, Lin, F, Richards, C, Barrett-Connor, E. Effect of postmenopausal hormone therapy on cognitive function: the Heart and Estrogen/progestin Replacement Study. Am J Med. 2002;113:543–548.CrossRefGoogle Scholar
33.Shumaker, SA, Legault, C, Thal, L, et al. Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women: the Women's Health Initiative Memory Study: a randomized controlled trial. JAMA. 2003;289:2651–2662.CrossRefGoogle ScholarPubMed
34.Rapp, SR, Espeland, MA, Shumaker, SA, et al. Effect of estrogen plus progestin on global cognitive function in postmenopausal women: the Women's Health Initiative Memory Study: a randomized controlled trial. JAMA. 2003;289:2663–2672.CrossRefGoogle ScholarPubMed
35.Aisen, PS, Davis, KL. Inflammatory mechanism in Alzheimer's disease: implications for therapy. Am J Psychiatry. 1994;151:1105–1113.Google ScholarPubMed
36.Aisen, PS, Davis, KL, Berg, JD, et al. A randomized controlled trial of prednisone in Alzheimer's disease. Alzheimer's Disease Cooperative Study. Neurology. 2000;54:588–592.CrossRefGoogle ScholarPubMed
37.Rogers, J, Kirby, LC, Hempelman, SR, et al. Clinical trial of indomethacin in Alzheimer's disease. Neurology. 1993;43:1609–1611.CrossRefGoogle ScholarPubMed
38.Scharf, S, Mander, A, Ugoni, A, Vajda, F, Christophidis, N. A double-blind, placebo-controlled trial of diclofenac/misoprostol in Alzheimer's disease. Neurology. 1999;53:197–201.CrossRefGoogle ScholarPubMed
39.Rich, JB, Rasmusson, DX, Folstein, MF, Carson, KA, Kawas, C, Brandt, J. Nonsteroidal anti-inflammatory drugs in Alzheimer's disease. Neurology. 1995;45:51–55.CrossRefGoogle ScholarPubMed
40.Stewart, WF, Kawas, C, Corrada, M, Metter, EJ. Risk of Alzheimer's disease and duration of NSAID use. Neurology. 1997;48:626–632.CrossRefGoogle ScholarPubMed
41. in t' Veld, BA, Ruitenberg, A, Hofman, A, et al. Nonsteroidal anti-inflammatory drugs and the risk of Alzheimer's disease. N Engl J Med. 2001;345:1515–1521.CrossRefGoogle Scholar
42.Etminan, M, Gill, S, Samii, A. Effect of non-steroidal anti-inflammatory drugs on risk of Alzheimer's disease: systematic review and meta-analysis of observational studies. BMJ. 2003;327:128.CrossRefGoogle ScholarPubMed
43.Martin, BK, Meinert, CL, Breitner, JC; ADAPT Research Group. Double placebo design in a prevention trial for Alzheimer's disease. Control Clin Trials. 2002;23:93–99.CrossRefGoogle Scholar
44.Weggen, S, Eriksen, JL, Das, P, et al. A subset of NSAIDs lower amyloidogenic Abeta42 independently of cyclooxygenase activity. Nature. 2001;414:212–216.CrossRefGoogle ScholarPubMed
45.Wolozin, B, Kellman, W, Ruosseau, P, Celesia, GG, Siegel, G. Decreased prevalence of Alzheimer's disease associated with 3-hydroxy-3-methyglutaryl coenzyme A reductase inhibitors. Arch Neurol. 2000;57:1439–1443.CrossRefGoogle ScholarPubMed
46.Jick, H, Zornberg, GL, Jick, SS, Seshadri, S, Drachman, DA. Statins and the risk of dementia. Lancet. 2000;356:1627–1631.CrossRefGoogle ScholarPubMed
47.Rockwood, K. Kirkland, S. Hogan, DB, et al. Use of lipid-lowering agents, indication bias, and the risk of dementia in community-dwelling elderly people. Arch Neurol. 2002;59:223–227.CrossRefGoogle ScholarPubMed
48.Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002;360:7–22.CrossRefGoogle Scholar
49.Shepherd, J, Blauw, GJ, Murphy, MB, et al. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet. 2002;360:1623–1630CrossRefGoogle Scholar
50.Miller, JW, Green, R, Ramos, MI, et al. Homocysteine and cognitive function in the Sacramento Area Latino Study on Aging. Am J Clin Nutr. 2003;78:441–447.CrossRefGoogle Scholar
51.Joosten, E, Lesaffre, E, Riezler, R, et al. Is metabolic evidence for vitamin B-12 and folate deficiency more frequent in elderly patients with Alzheimer's disease? J Gerontol A Biol Sci Med Sci. 1997;52:M76–M79.CrossRefGoogle ScholarPubMed
52.McCaddon, A, Davies, G, Hudson, P, Tandy, S, Cattell, H. Total serum homocysteine in senile dementia of Alzheimer's type. Int J Geriatr Psychiatry. 1998;13:235–239.3.0.CO;2-8>CrossRefGoogle Scholar
53.Lehmann, M, Gottfries, CG, Regland, B. Identification of cognitive impairment in the elderly: homocysteine is an early marker. Dement Geriatr Cogn Disord. 1999;10:12–20.CrossRefGoogle ScholarPubMed
54.Seshadri, S, Beiser, A, Selhub, J, et al. Plasma homocysteine as a risk factor for dementia and Alzheimer's disease. N Engl J Med. 2002;346:476–483.CrossRefGoogle ScholarPubMed
55.Clarke, R, Smith, AD, Jobst, KA, Refsum, H, Sutton, L, Ueland, PM. Folate, vitamin B12, and serum total homocysteine levels in confirmed Alzheimer's disease. Arch Neurol. 1998;55:1449–1455.CrossRefGoogle Scholar
56.Budge, M, Johnston, C, Hogervorst, E, et al. Plasma total homocysteine and cognitive performance in a volunteer elderly population. Ann N Y Acad Sci. 2000;903:407–410.CrossRefGoogle Scholar
57.Aisen, PS, Egelko, S, Andrews, H, et al. A pilot study of vitamins to lower plasma homocysteine levels in Alzheimer's disease. Am J Geriatr Psychiatry. 2003;11:246–249.CrossRefGoogle Scholar